Molecular mechanism of Ca^<2+> channel activation by phosphorylation : functional regulation by phosphorylation of channel subunit CACNA1C
| Project/Area Number |
15590231
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Nagasaki University |
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Principal Investigator |
KAIBARA Muneshige Nagasaki Univ., Grad.Sch.Biomed.Sci., Ass.Prof., 大学院・医歯薬学総合研究科, 助教授 (40274633)
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| Co-Investigator(Kenkyū-buntansha) |
TANIYAMA Kohtaro Nagasaki Univ., Grad.Sch.Biomed.Sci., Prof., 大学院・医歯薬学総合研究科, 教授 (70030898)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | L-type / calcium channel / phosphorylation / A-kinase / alpha subunit / beta subunit / BHK / patch clamp / phosphrylation / protein kinase A / H-89 / aJpha subunit / BHK cell / カルシュウムチャネル / α1c / CACNA1C / リン酸化 / 遺伝子治療 / 心筋 |
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| Research Abstract |
Background : Ca^<2+> channel & beta ; subunit plays an important role in an enhancement of the channel function. A possibility of a gene therapy using & beta ; subunit for the failing heart is postulated. The purpose of this study was to clarify the functional interaction of & beta ; subunit with pore forming & alpha;1c subunit. Methods : Calcium channel alpha 1c (0.5 ng) subunit with selected concentrations of beta 2a subunit were cotransfected into BHK cells : & beta;2a/ & alpha;1c=0/5,1/5,5/1(mole concentration ratio). The expressed Ca^<2+> channels currents were recorded using the whole-cell patch clamp method with 40mM Ba^<2+>. cAMP (1 mM) was added in the pipette solution to observe the cAMP-PKA-mediated phosphorylation. Results and conclusion : 1)current enhancement with beta 2a subunit was dose-dependent, 2)activation kinetics shift toward negative potential with beta 2a, 3)steady-state inactivation kinetics were not affected with beta 2a, 4)no significant enhancement of the current by cAMP was observed in the cells over expressing beta 2a. Our data indicate that calcium channel beta 2a subunit regulates activation gate of alpha 1c and modulates the cAMP-PKA-mediated regulation.
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Report
(3 results)
Research Products
(16 results)
